olaparib maintenance with pembrolizumab & bevacizumab in brca non-mutated patients with platinum-sensitive recurrent ovarian cancer

Conditions: Platinum-sensitive Recurrent BRCA Wild Type Ovarian Cancer

Summary: this study is phase ii, open label, clinical trial to determine the efficacy of olaparib maintenance with bevacizumab and pembrolizumab by assessment progression-free survival(6 months pfs rate) in brca non-mutated patients with platinum-sensitive recurrent ovarian cancer.

'this is a phase ii, open-label, non-randomized, multi-center study assessing the efficacy and safety of olaparib maintenance with bevacizumab and pembrolizumab in subjects with platinum-sensitive who have received prior of platinum-based chemotherapy. the study will assess the effectiveness of progression-free survival(6 months pfs rate) as determined by response evaluation criteria in solid tumors (recist) v1.1. the subject will be treated to until disease progression as below: * maintenance : olaparib 300mg (twice daily \[bid\]) * pembrolizumab 200mg every 3 weeks (q3w) from 2nd infusion for up to 35 infusions * bevacizumab 15mg/kg or 7.5mg/kg every 3 weeks (q3w)

Eligibility criteria:
inclusion criteria: * participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous oc, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 8 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included). * participant has received 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 months' period between penultimate platinum regimen and progression of disease * participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen * participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of brca 1/2 and pd-l1 status prior to enrollment * female participants who are at least 20 years of age and eastern cooperative oncology group (ecog) performance status of 0 or 1 * participant has adequate organ function as defined in the following: 1. anc≥1500/µl 2. plt≥100 000/µl 3. hemoglobin≥9.0 g/dl or ≥5.6 mmol/l 4. creatinine≤1.5 × uln or calculated creatinine clearance≥30 ml/min for participant with creatinine levels \>1.5 × institutional uln 5. total bilirubin≤1.5 ×uln or direct bilirubin ≤uln for participants with total bilirubin levels \>1.5 × uln 6. ast (sgot) and alt (sgpt)≤2.5 × uln (≤5 × uln for participants with liver metastases) 7. international normalized ratio (inr) or prothrombin time (pt), activated partial thromboplastin time (aptt)≤1.5 × uln unless participant is receiving anticoagulant therapy as long as pt or aptt is within therapeutic range of intended use of anticoagulants exclusion criteria: * participant has mucinous, germ cell, or borderline tumor of the ovary * participant has a known or suspected deleterious mutation (germline or somatic) in either brca1 or brca2 * participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis * participant either has myelodysplastic syndrome (mds)/ acute myeloid leukemia (aml) or has features suggestive of mds/aml * participant has a known additional malignancy that is progressing or has required active treatment within the past 3 years * participant has known active cns metastases and/or carcinomatous meningitis * participant has a known history of active tb (bacillus tuberculosis) * participant has a known history of hepatitis b (defined as hepatitis b surface antigen \[hbsag\] reactive) or known active hepatitis c virus (defined as hcv rna \[qualitative\] is detected) infection * participant has uncontrolled hypertension, defined as systolic \> 140 mmhg or diastolic \> 90 mmhg documented by 2 blood pressure readings taken at least 1 hour apart * participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization

Keywords: brca wild type ovarian cancer platinum-sensitive